In a retrospective cohort study reported in JAMA Oncology by Allison W. Kurian, MD, of Stanford University School of Medicine, and colleagues found that use of germline multiple-gene sequencing has become more common than BRCA1/2-alone sequencing after breast cancer diagnosis in clinical practice.

The study involved surveys of 5,026 patients (representing a 70% response rate in the entire population) diagnosed with breast cancer from January 2013 to December 2015 in Surveillance, Epidemiology, and End Results (SEER) registries in Georgia and Los Angeles. Responses were merged with SEER data and results of clinical genetic testing consisting of BRCA1 and BRCA2 (BRCA1/2) sequencing alone or multiple-gene sequencing provided by four laboratories.

Among the 5,026 patients, 1,316 (26.2%) were linked to genetic results from any laboratory. Whereas multiple-gene sequencing accounted for 25.6% of tests and BRCA1/2-alone testing, 74.4% in 2013, the proportions had changed to 66.5% vs 33.5% in 2015. Multiple-gene sequencing was most often ordered by genetic counselors (25.5% vs 15.3% BRCA1/2-only testing) and was more commonly delayed until after surgery (32.5% vs 19.9% for BRCA1/2-alone testing).

Multiple-gene sequencing was associated with increased detection of any pathogenic variant vs BRCA1/2-alone testing among higher-risk patients (12% vs 7.8%) and average-risk patients (4.2% vs 2.2%) and increased detection of variants of uncertain significance, with detection rates of 23.7% vs 2.2% in white patients, 44.5% vs 5.6% in black patients, and 50.9% vs 0% in Asian patients. Multiple-gene sequencing was not associated with an increased use of prophylactic mastectomy, with the rate of such treatment being highest in patients with BRCA1/2 pathogenic variants, followed by other pathogenic variants (37.6%), variants of uncertain significance (30.2%), and no pathogenic variants or variants of uncertain significance (35.3%).

The investigators concluded, “Multiple-gene sequencing rapidly replaced BRCA1/2-only testing for patients with breast cancer in the community and enabled 2-fold higher detection of clinically relevant pathogenic variants without an associated increase in prophylactic mastectomy. However, important targets for improvement in the clinical utility of multiple-gene sequencing include postsurgical delay and racial/ethnic disparity in variants of uncertain significance.” ■